Achieving Glycemic Control in

T2DM Based on Recent Guideline

Speaker Name

For Healthcare Professional Only

Disclosure
I have received honorarium as speaker/consultant, support for research/attendance at educational
meetings from:
• Novo Nordisk
• …………
Agenda

Insulin Treatment

Indonesia Situation Guideline Insulin Option

Recommendation
Agenda

Insulin Treatment

Indonesia Situation Guideline Insulin Option

Recommendation
Diabetes is one of the most pressing health challenges of the
decade, including in Indonesia

Indonesia #5 in the world of T2DM cases

3 in 4
537 adults with 6.7
million diabetes live million Number of people with diabetes (millions)
adults are living in low- and deaths due to
with diabetes middle- income diabetes in 2021 Brazil 15.7
countries
Indonesia 19.5

USA 32.2

Pakistan 33

India 74.2

China 140.9

0 20 40 60 80 100 120 140 160

Number of people with diabetes (millions)

References
1. International Diabetes Federation. IDF Diabetes Atlas. 10th edn. Brussels, Belgium: International Diabetes Federation. 2021.
As a 5th biggest Diabetes countries, Indonesia still have a lot of
undiagnosed patients and only few were treated

74% were 8% were

27.7 undiagnosed1 treated in FKRTL2

10.3

0.8
2.7

Prediabetes Diabetes Diagnosed Treated (in FKRTL2)

References:
1. International Diabetes Federation. IDF Diabetes Atlas. 8th edn. Brussels, Belgium: International Diabetes Federation. 2017
2. Cost of Illness Study. Budi Hidayat, et al. 2019. Study conducted based on BPJS database 2016: INA-CBGs + PRB, FKTP not included.
And compared with neighboring countries, Indonesia is one of the
highest HbA1c
Mean HbA1c (%)

Indonesian HbA1c is
the highest compared with

9.2% other participant countries

in DISCOVER study (n=221),
even after initiating second line of
therapy (mean+SD = 9.2+2%)1,
almost 70% patient >8%).2

Reference:
1. Ji L et al. 53rd EASD, 11–15 September 2017, Lisbon, Portugal.
2. Soeatmadji DW et al. 2nd ICE on IMERI, 7 November 2017, Jakarta, Indonesia
Agenda

Insulin Treatment

Indonesia Situation Guideline Insulin Option

Recommendation
 9

Insulin remains the most efficacious glucose lowering agent

Decrease in HbA1c: Potency of monotherapy

HbA1c %

Nathan et al., Diabetes Care 2009;32:193-203.

 10

Every 1% drop in HbA1c can reduce long-term diabetes complications1

43% 37% 19% 16% 14% 12%

Stroke
Myocardial infarction
Heart failure
Cataract extraction

Microvascular disease

Lower extremity
amputation or fatal
peripheral vascular
disease

References: 1. Stratton IM et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-412.
Insulin treatment attempts to mimic the pattern
of normal insulin secretion
Short-lived, rapidly generated Overall aim of insulin therapy
70 meal-related insulin peaks To achieve near-normal glucose
control (normoglycaemia), ie, blood
60 glucose not too high nor too low
Insulin (µU/mL)

50

40

30 Low, steady, basal

insulin profile
20

10

0
6:00 10:00 14:00 18:00 22:00 2:00 6:00
Time of day

Adapted from Polonsky KS et al. J Clin Invest. 1988;81:442–8.

 Analogue insulins
Rapid-acting Long-acting Ultra long-acting Premixed Co-Formulation

• Absorbed more • Background • Background • Mixture of • Mixture of

rapidly, shorter insulin, insulin, rapid- & ultra long
duration of more slowly more slowly intermediate- acting and
action than absorbed absorbed acting insulin rapid acting
short-acting (30/70, insulin (70/30)
human insulins • Provide basal • Provide basal 25/75,50/50)
level of insulin level of insulin • Providing 24
• Aim to control throughout day throughout day hours basal
postprandial and night for and night for 24 coverage and
glucose up to 24 hours hours (and up to post prandial
36–42 hours) glucose

Please refer to the relevant product summary of product characteristics (SmPC) for full pharmacological information .
 Insulin regimen
When trying to recreate the normal pattern of insulin secretion,
different patients have different needs in terms of:
• Number of injections
• Timing of injection
• Type of insulin

Basal only Basal-bolus Premixed Co-Formulation

• Long-acting:
Mealtimes and
1x per day
bedtime 1, 2 or 3x per day 1 or 2 times per day
• Intermediate-acting:
(4x per day)
1–2x per day

See individual summary of product characteristics (SmPC) for specific prescribing information.
1. Royal College of Nursing. Starting injectable treatment in adults with type 2 diabetes, 3rd edition. 2019. https://www.rcn.org.uk/-/media/royal-college-of-nursing/documents/publications/2019/november/
007-758.pdf?la=en. Accessed 10 November 2020;
2. Patient. Insulin regimens. Available at https://patient.info/doctor/insulin-regimens. Accessed 10 November 2020.
 Basal insulin: once-daily
Duration of action depends
Basal human insulin
on the insulin type
Basal analogue insulin
NPH (intermediate human
13–18 h insulin)
More pronounced peak activity1
Insulin action

Long-acting analogue
Up to 24 h insulins

Ultra-long acting analogue

Beyond 24 h insulins

Insulin injection Time

Schematic representation of a once-daily insulin injection.

h, hours; NPH, neutral protamine hagedorn; SmPC, summary of product characteristics.
1. Lindholm A. Best Pract Res Clin Gastroenterol. 2002;16:475–92.
 Basal–bolus insulin regimen
Rapid Rapid Rapid Long
insulin insulin insulin insulin

Rapid-acting insulin

Short-acting
human insulin
Rapid-acting analogue
Insulin action

insulin

Long-acting insulin

Intermediate-acting
human insulin
Long-acting analogue
insulin

Breakfast Lunch Dinner Bedtime

Schematic representation of four injections per day (one long-acting, three rapid-acting).
 Premixed insulin: once, twice or three times daily
Premixed human insulin Two components
Premixed analogue insulin
Premixed injection Premixed injection Short-acting/
Intermediate
rapid-acting

Possible regimens (daily)

Insulin action

1 2 3
Each meal
Largest meal Dinner and
(breakfast, lunch,
(usually dinner) breakfast
dinner)

Breakfast Lunch Dinner

Schematic representation of twice-daily insulin injections.

Owens DR. Diabet Med. 2013;30:276–288.
 Co-Formulation once or twice daily

Glucose-lowering effect of Co-Formulation given once daily

IDegAsp 0.6 kg/U OD

Prandial Coverage

Basal Coverage

1. Haahr H et al. Clin Pharmacokinet 2017;56(4):339–354

Agenda

Insulin Treatment

Indonesia Situation Guideline Insulin Option

Recommendation
 Algoritma Penatalaksanaan DMT2 tanpa Dekompensasi Metabolik
(sasaran kendali glukosa darah HbA1C < 7% /individualisasi)

Guideline Perkeni 2021. Pedoman Pengelolaan dan Pencegahan DMT2

 Initiation
ALGORITHM
Insulin
Therapy Basal
Co-Formulation
FRC
or Premixed
Patients Type 2 DM + oral
(mono/dual/triple) Dose 10U at night or
0.2 unit/kg/BW
HbA1C > 7.5%

Maximum dose
0.5 unit/kg/BW

Intensification

Titrasi:
Target:
(Jika nilai GDP atau pre-prandial)
GDP/ Pre-prandial: 80-130 mg/dL
> 180 mg/dL : +4 Unit
GDP 1 – 2 PP : <180 mg/dL
130 – 180 mg/dL : +2 Unit
HbA1C : <7% (evaluasi 3 bulan)
< 130 mg/dL : dosis tetap

Guideline Perkeni 2021. Pedoman Terapi Insulin pada Pasien Diabetes Melitus.
 Intensification

Basal Co-Formulation FRC

ALGORITHM Basal
or Premixed
FRC

Insulin FPG or Pre-prandial breakfast FPG or Pre-prandial breakfast FPG or Pre-prandial breakfast
Therapy NORMAL ;
Lunch blood glucose
INCREASE ;
Lunch blood glucose
INCREASE ;
Lunch blood glucose
INCREASE NORMAL INCREASE
Patients Type 2 DM + oral
+
(mono/dual/triple) +GLP1RA
prandial

HbA1C > 7.5% Premixed

BID > TID
BASAL PLUS
1>2>3

Basal Bolus

Titrasi:
Target:
(Jika nilai GDP atau pre-prandial)
GDP/ Pre-prandial: 80-130 mg/dL
> 180 mg/dL : +4 Unit
GDP 1 – 2 PP : <180 mg/dL
130 – 180 mg/dL : +2 Unit
HbA1C : <7% (evaluasi 3 bulan)
< 130 mg/dL : dosis tetap

Guideline Perkeni 2021. Pedoman Terapi Insulin pada Pasien Diabetes Melitus.
 Initiation

ALGORITHM
Insulin Co-Formulation FRC Basal Plus Basal Bolus
Therapy
+ Prandial at the largest meal + Prandial at the third meal.
Starting dose 10 Unit Starting dose 10 Unit
Patients Type 2 DM NEW Basal at night Basal at night
HbA1C > 9%;
FPG >250 mg/dL ; Starting dose prandial
4U/hari or 10% from
Basal 10U (bedtime)
BG > 300 mg/dl; basal dose
Prandial 4U

Metabolic Decompensation
Dose optimalization Dose optimalization
OD  BID OD  BID Optimalization dose

De-escalation

Intensification

Titrasi:
Target:
(Jika nilai GDP atau pre-prandial)
GDP/ Pre-prandial: 80-130 mg/dL
> 180 mg/dL : +4 Unit
GDP 1 – 2 PP : <180 mg/dL
130 – 180 mg/dL : +2 Unit
HbA1C : <7% (evaluasi 3 bulan)
< 130 mg/dL : dosis tetap

Guideline Perkeni 2021. Pedoman Terapi Insulin pada Pasien Diabetes Melitus.
 Intensification
ALGORITHM
Insulin
Therapy
CO-FORMULATION
or
Basal-Plus
Basal
FIX-RATIO Bolus
COMBINATION
Patients Type 2 DM NEW
HbA1C > 9%;
FPG >250 mg/dL ;
BG > 300 mg/dl;
Metabolic Decompensation BASAL PLUS
+ prandial Basal Plus 1>2>3

Basal Bolus

Titrasi:
Target:
(Jika nilai GDP atau pre-prandial)
GDP/ Pre-prandial: 80-130 mg/dL
> 180 mg/dL : +4 Unit
GDP 1 – 2 PP : <180 mg/dL
130 – 180 mg/dL : +2 Unit
HbA1C : <7% (evaluasi 3 bulan)
< 130 mg/dL : dosis tetap

Guideline Perkeni 2021. Pedoman Terapi Insulin pada Pasien Diabetes Melitus.
FORNAS 2021

Halaman 103 – 104

Untuk Pasien Diabetes Tipe 2
FORNAS terbaru berlaku 1 Januari 2022
Insulin basal & campuran dapat dimulai apabila

1 Pasien diabetes melitus tipe 2 2 Pasien diabetes melitus tipe 2

Belum terkontrol dengan HbA1c > 9%

kombinasi metformin dosis optimal & OAD lain

HbA1c > 7.5% Gejala dekompensasi metabolik

Rerata gula darah 169 mg/dl

Pemberian insulin pada (1) dan (2) dapat dilanjutkan untuk pasien diabetes melitus tipe 2, jika insulin dibutuhkan untuk mempertahankan
pengendalian glukosa darah.

Formularium Nasional 2021

Agenda

Insulin Treatment

Indonesia Situation Guideline Insulin Option

Recommendation
27

Our insulin options

Human Insulin Analog Insulin New Generation Insulin

Intermediate Acting Long-Acting Ultra Long-Acting

• Humulin® N • Glargine • Degludec*
• Insulatard® • Detemir* • Glargine U300
Short Acting Rapid Acting Rapid Acting
• Humulin® R • Lispro • Faster Aspart
• Actrapid® • Aspart*
Mix • Gluisin Co-formulation/FRC
• 70/30 Humulin® Mix • IDegAsp
• 70/30 Mixtard® • Protamin lispro • IGlarLixi
• Protamine Aspart • IDegLira
GREEN: Available in JKN
BLUE: Not available in JKN Guideline Perkeni 2021. Pedoman Terapi Insulin pada Pasien Diabetes Melitus.
*Data pregnancy available
Detemir
A soluble, basal insulin analogue
Produced in Saccharomyces Cerevisiae, recombinant DNA
technology
How does it work?
• Detemir is a basal insulin analogue (covering FPG)
with a prolonged duration of effect (up to 24 hours).
• Compared to other insulin products, basal-bolus
therapy with Detemir is not associated with weight
gain.
Indication
• Treatment of diabetes mellitus in adults, adolescents
and children aged 2 years and above.
Levemir Product Information, 2022
Composition
• 1 ml of the solution contains 100 U of insulin detemir* (equivalent to 14.2 mg)
• Solution for injection - Subcutaneous administration
Presentations
• Clear, colourless, neutral solution for injection in pre-filled pen (FlexPen)
• 1 pre-filled pen contains 3 ml equivalent to 300 U
Dosage
• When Detemir is used in combination with oral antidiabetic medicinal products or
when added to liraglutide or lixisenetide, it is recommended to use Detemir once
daily, initially at a dose of 0.1 – 0.2 U/kg, or of 10 U in adult patients.
• The dose of Detemir should be titrated based on the individual patient’s needs.
Storage:
Before opening: Store in a refrigerator (2°C – 8°C). Keep away from the cooling element. Do
not freeze. Keep the pen cap on to protect from light. During use or when carried as a spare:
Store below 30°C. Can be stored in a refrigerator
(2°C – 8°C). Use within 6 weeks. Do not freeze
Aspart
A Rapid Acting Insulin Analogue
Produced in Saccharomyces Cerevisiae, recombinant DNA
technology
How does it work?
• Rapid Acting insulin – absorbed faster by the body
than human insulin
• Helps glucose enter cells from the blood
• Can be used with an intermediate or
long-acting insulin given at least once a day
• Designed to better mimic the normal insulin
response to changes in blood sugar levels
Indication
• Treatment of diabetes mellitus in adults, adolescents
and children aged 2 years and above.
Novorapid Product Information, 2021
Composition
• 1 ml of the solution contains 100 U of insulin aspart* (equivalent to 3.5 mg)
• Solution for injection - Subcutaneous administration
Presentations
• Clear, colourless, aqueous solution for injection in pre-filled pen (FlexPen)
• 1 pre-filled pen contains 3 ml equivalent to 300 U
Dosage
• Dosage is individual and determined on the basic of the physician’s advice in
accordance with the needs of the patient. It should normally be used in combination
with intermediate-acting or long-acting insulin given at least once a day. Blood
glucose monitoring and insulin dose adjustment are recommended to achieve optimal
glycaemic control.
Storage:
Before opening: Store in a refrigerator (2°C – 8°C). Keep away from the cooling element.
During use or when carried as a spare: Store below 30°C. Can be stored in a refrigerator (2°C
– 8°C). Use within 4 weeks. Do not freeze.
Premix Aspart (insulin aspart*/protamine-crystallised aspart*)
Produced in Saccharomyces Cerevisiae, recombinant DNA technology
How does it work?
• Insulin aspart is fast-acting (within 10-20 minutes of
injection)
• Protamine-crystallised form is intermediate acting
Indication
• Treatment of diabetes mellitus in adults,
• Can be used in children and adolescents aged 10
years and above with type 1 diabetes mellitus when
premixed insulin is preferred.
Novomix 30 Product Information, 2021
Composition
• 1 ml of the suspension contains 100 U of soluble insulin aspart*/protamine-crystallised
insulin aspart* in the ratio 30/70
• Suspension for injection - Subcutaneous administration
Presentations
• White suspension for injection in a pre-filled pen (FlexPen)
• 1 pre-filled pen contains 3 ml equivalent to 300 U
• Mixed well before use
Dosage
• Dosage is individual and determined in accordance with the needs of the patient.
Blood glucose monitoring and insulin dose adjustments are recommended to achieve
optimal glycaemic control.
• For patients with type 2 diabetes, the recommended starting dose is 6 U at breakfast
and 6 U at dinner. However, it can also be initiated once daily with 12 U at dinner
(evening meal).
Storage
When not in use: Store in a refrigerator (2°C – 8°C). Keep away from the cooling
element. Do not freeze.
Storage during use or when carried as a spare: not to be kept in the refrigerator. It can be kept
at room temperature (below 30°C) for up to 4 weeks
IDegAsp
New Generation Insulin contain ultra-long and rapid acting
insulin in one pen.
Produced in Saccharomyces Cerevisiae, recombinant DNA
technology
How does it work?
• IDegAsp is a soluble insulin product consisting of
insulin degludec and insulin aspart that can cover
both basal and prandial glucose
Indication
• Treatment of diabetes mellitus in adults, adolescents
and children from the age of 2 years
Ryzodeg 30 Product Information, 2022
Composition
• 1 ml solution contains 100 units insulin degludec/insulin aspart* in the ratio 70/30. One
pre-filled pen contains 300 units of insulin degludec/insulin aspart in 3 ml solution
• Solution for injection - Subcutaneous administration
Presentations
• FlexTouch (pre-filled pen) that compatible with most needles including NovoFine®
needles. FlexTouch provide easy-to-read dose display, non-extending button to make it
easier to inject, and An audible ‘click’ sound indicates that full insulin dose has been
delivered.
Dosage
• T2DM: IDegAsp can be administered once or twice daily with the main meal(s)
alone, in combination with oral antidiabetic medicinal products, and in combination
with bolus insulin
• T1DM: IDegAsp® can be administered once daily at mealtime in combination with
short-/rapid acting insulin at the remaining meals
Storage:
Opened pens 2–8°C or room temperature for 4 wks. Unopened pens 2–8°C until expiry date